Inflammasomes as therapeutic targets in human diseases
Abstract Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-021-00650-z |
| _version_ | 1818622021437751296 |
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| author | Yangxin Li Hui Huang Bin Liu Yu Zhang Xiangbin Pan Xi-Yong Yu Zhenya Shen Yao-Hua Song |
| author_facet | Yangxin Li Hui Huang Bin Liu Yu Zhang Xiangbin Pan Xi-Yong Yu Zhenya Shen Yao-Hua Song |
| author_sort | Yangxin Li |
| collection | DOAJ |
| description | Abstract Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy. |
| first_indexed | 2024-12-16T18:18:33Z |
| format | Article |
| id | doaj.art-41b4364aa6a24f829e403a8d74f75df9 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-12-16T18:18:33Z |
| publishDate | 2021-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-41b4364aa6a24f829e403a8d74f75df92022-12-21T22:21:38ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-07-016111410.1038/s41392-021-00650-zInflammasomes as therapeutic targets in human diseasesYangxin Li0Hui Huang1Bin Liu2Yu Zhang3Xiangbin Pan4Xi-Yong Yu5Zhenya Shen6Yao-Hua Song7Institute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, Collaborative Innovation Center of Hematology, Soochow UniversityCardiovascular Department, The Eighth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Cardiology, The Second Hospital of Jilin UniversityInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, Collaborative Innovation Center of Hematology, Soochow UniversityDepartment of Cardiac Surgery, Fuwai HospitalKey Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, Guangzhou Medical UniversityInstitute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, Collaborative Innovation Center of Hematology, Soochow UniversityCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityAbstract Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy.https://doi.org/10.1038/s41392-021-00650-z |
| spellingShingle | Yangxin Li Hui Huang Bin Liu Yu Zhang Xiangbin Pan Xi-Yong Yu Zhenya Shen Yao-Hua Song Inflammasomes as therapeutic targets in human diseases Signal Transduction and Targeted Therapy |
| title | Inflammasomes as therapeutic targets in human diseases |
| title_full | Inflammasomes as therapeutic targets in human diseases |
| title_fullStr | Inflammasomes as therapeutic targets in human diseases |
| title_full_unstemmed | Inflammasomes as therapeutic targets in human diseases |
| title_short | Inflammasomes as therapeutic targets in human diseases |
| title_sort | inflammasomes as therapeutic targets in human diseases |
| url | https://doi.org/10.1038/s41392-021-00650-z |
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